A Drug-Food Interaction Study Between Colchicine and Grapefruit Juice

Pharmacokinetics Clinical Trial

Official title:

A One-Directional, Open-Label Drug-Food Interaction Study to Investigate the Effects of Multiple-Daily Consumptions of Grapefruit Juice on the Single-Dose Pharmacokinetics of Colchicine in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00984009
• Other study ID #: MPC-004-08-1017
• Status: Completed
• Phase: Phase 1
• First received: August 13, 2009
• Last updated: November 11, 2011
• Start date: September 2008
• Est. completion date: October 2008

Study information

• Verified date: November 2011
• Source: Mutual Pharmaceutical Company, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Grapefruit juice is an inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple daily consumptions of grapefruit juice on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period.

Description:

Grapefruit juice is an inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple daily consumptions of grapefruit juice on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. On study Day 1, after a fast of at least 10 hours twenty-two healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one dose of colchicine (1 x 0.6 mg tablet). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of colchicine. Blood sampling will continue on a non-confined basis on Days 2-5. After a 14 day washout period, starting on the morning of Day 15 and continuing through Day 17, subjects will return to the clinic for consumption of an administered dose of grapefruit juice (1 x 240 ml) twice daily. On the morning of Day 18 after a fast of at least 10 hours all subjects will receive a co-administered single oral dose of colchicine (1 x 0.6 mg) and grapefruit juice (1 x 240 ml). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of colchicine in the presence of grapefruit juice. Blood sampling will continue on a non-confined basis on Days 19-22. Subjects will consume the final administered dose of grapefruit juice (1 x 240 ml) in the evening on Day 18. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Seated blood pressure and pulse will be measured prior to dosing and at approximately 1, 2, and 3 hours following drug administration on Days 1 and 18 to coincide with peak plasma concentrations of colchicine. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the Investigator and reported in the subject's case report form.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy adults 18-45 years of age, non-smoking and non-pregnant (post-menopausal, surgically sterile or using effective contraceptive measures) with a body mass index (BMI) greater than or equal to 18 and less than or equal to 32, inclusive.

Exclusion Criteria:

• Recent participation (within 28 days) in other research studies

• Recent significant blood donation or plasma donation

• Pregnant or lactating

• Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)

• Recent (2-year) history or evidence of alcoholism or drug abuse

• History or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease

• Subjects who have used any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-glycoprotein (P-gp) within 28 days prior to the first dose and throughout the study

• Drug allergies to colchicine

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Drug:
• Colchicine
A single dose of 0.6 mg colchicine administered alone at 7:15 a.m. on Day 1

Other:
• Grapefruit Juice
240 mL of grapefruit juice ingested twice daily at 7:15 a.m. and 7:15 p.m. on Days 15 to 18.

Drug:
• Colchicine
A single dose of 0.6 mg colchicine administered with grapefruit juice at 7:15 a.m. on Day 18 after an overnight fast of at least 10 hours.

Locations

Country	Name	City	State
United States	PRACS Institute, Ltd. - Cetero Research	Fargo	North Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Mutual Pharmaceutical Company, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax)	The maximum or peak concentration that colchicine reaches in the plasma.	serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 18, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration	No
Primary	Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]	The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable colchicine concentration (t), as calculated by the linear trapezoidal rule.	serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 18, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration	No
Primary	Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-8)]	The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-8) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable colchicine plasma concentration to the elimination rate constant.	serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 18, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 hours after colchicine dose administration	No

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